Tuesday, November 14, 2006
Mother's Diet during Pregnancy can affect Grandchildren (Epigenetics)
A new study by scientists at Children's Hospital Oakland Research Institute (CHORI) is the first to show that a mother's diet during pregnancy influences the health of her grandchildren by changing the behavior of a specific gene. The study was conducted using mice of an unique strain called 'viable yellow agouti' also known as A-vy in scientific terms. These mice possesss a gene that influences the color of their coats as well as their tendency to become obese and develop diabetes and cancer. The new research shows that the diet consumed by a pregnant Avy mouse affects the health of not only her pups, but also their pups - her grandchildren.
The study was published in the November issue of the Proceedings of the National Academy of Sciences (PNAS) and was conducted by CHORI Scientist David Martin, M.D., and Assistant Scientist Kenneth Beckman, Ph.D., in collaboration with Drs. Jennifer Cropley and Catherine Suter from the Victor Chang Heart Institute in Sydney, Australia. In their experiments, the scientists fed some Avy mice a standard lab diet based on common foods consumed by humans. Other mice were fed this same diet supplemented with common nutritional supplements including folate, choline, betaine, vitamin B12, zinc and methionine.
The supplements were fed to the mice for a week during mid-pregnancy. The offspring were examined for their coat color, and female offspring were themselves mated again (without a supplemented diet) to produce a third generation of 'grandchildren.' The results showed that the supplements changed the behavior of the agouti gene in the first generation of pups, shifting their coats towards a brown color, and had the same effect on pups born in the next generation to mice that were not exposed to the supplemented diet.
"Although researchers have long known that there is a connection between a mother's diet and her children's health this is the first case in which the relationship between a mother's diet and the biology of her grandchildren has been mapped to a single gene and a defined diet," said David Martin, M.D., Scientist at CHORI. "Our work provides convincing evidence of complex transgenerational effects of nutrition on health, and provides an experimental model for exploring these relationships in detail."
Avy mice are an excellent system for study because all mice of this strain are genetically identical - as similar to each other as identical twins. However, mouse pups from a single litter differ from each other in their coat color (from yellow to brown), obesity (thinner to fatter), and susceptibility to cancer, and all of these varied traits can be traced back to the Avy version of the agouti gene. The mouse model also suggests that similar things can happen in humans, since our gene characteristics are very similar.
Although this study does not provide any prescriptive advice, it does offer significant evidence that health outcomes may be strongly influenced at the time of birth. "Our study highlights a layer of complexity about human development that needs to be thoroughly investigated," said Kenneth Beckman, Ph.D. Assistant Scientist at CHORI and a member of the Project EXPORT Center of Excellence in Nutritional Genomics, a PROGRAM PROJECT funded by the National Center on Minority Health and Health Disparities. "We found that even when we stopped providing specific supplements during pregnancy, the past effect of supplements persisted. Therefore, it is possible that the maternal diet could have implications that stretch over decades, perhaps even centuries."
Based on the PNAS paper:
Germ-line epigenetic modification of the murine A-vy allele by nutritional supplementation
Jennifer E. Cropley, Catherine M. Suter, Kenneth B. Beckman, and David I. K. Martin
PNAS | November 14, 2006 | vol. 103 | no. 46 | 17308-17312
Environmental effects on phenotype can be mediated by epigenetic modifications. The epigenetic state of the murine Avy allele is highly variable, and determines phenotypic effects that vary in a mosaic spectrum that can be shifted by in utero exposure to methyl donor supplementation. We have asked if methyl donor supplementation affects the germ-line epigenetic state of the Avy allele. We find that the somatic epigenetic state of Avy is affected by in utero methyl donor supplementation only when the allele is paternally contributed. Exposure to methyl donor supplementation during midgestation shifts Avy phenotypes not only in the mice exposed as fetuses, but in their offspring. This finding indicates that methyl donors can change the epigenetic state of the Avy allele in the germ-line, and that the altered state is retained through the epigenetic resetting that takes place in gametogenesis and embryogenesis. Thus a mother's diet may have an enduring influence on succeeding generations, independent of later changes in diet. Although other reports have suggested such heritable epigenetic changes, this study demonstrates that a specific mammalian gene can be subjected to germ-line epigenetic change.
See "Cardiovascular and diabetes mortality determined by nutrition" (very relevant - don't be misled by the title!)
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